This invention relates to aspartic acid derivatives and their salts.
In peptide synthesis, .omega.-carboxyl groups or .alpha.-carboxyl groups must normally be protected. Regarding the protecting groups for the .omega.-carboxyl groups of dicarboxylamino acids (such as aspartic acid, glutamic acid, .alpha.-aminoadipic acid and .alpha.-aminopimetic acid), it is necessary to selectively cleave the .alpha.-carboxyl protecting groups of these amino acids. In the past, benzyl group which is stable against acids such as trifluoroacetic acid and can be removed by catalytic reduction or t-butyl group which is stable against catalytic reduction and can be removed with an acid was frequently used as a protecting group for .omega.-carboxyl group but several technological problems have been noted and there has been an increased demand for development of superior protecting groups.
More in detail, benzyl group has been frequently used as the protecting group for .omega.-carboxyl group in peptide synthesis but it is known that succinimide formation takes place during the condensation or deprotection reaction. If the peptides contain aspartyl-glycine or aspartyl-serine linkage, in particular, such side reactions become dominant and it is difficult to obtain a high yield of the target substance. This phenomenon was reported also in the case of glutamic acid, for example, by Battersby, et al. (J. Chem. Soc., pp. 259-269 (1955)) and Hanson, et al (ibid., pp. 836-842 (1964)). Use has also been made frequently of t-butyl group but it is difficult to introduce t-butyl group into carboxyl group and it can be applied industrially only to a limited extent (Katsoyannis, et al., "Methods In Enzymology", Vol. 47, Part E. "Enzyme Structure", pp. 529-532, Academic Press, New York (1977)). As for the hydrogen fluoride method which has conventionally been used as the method of final deprotection whereby all protecting groups are removed, it is recently pointed out that there are various problems of side reactions which are difficult to eliminate (B. Ridge, "Amino-Acids Peptides and Proteins", The Chemical Society, Vol. 6, p. 302 (1975)). Thus, methods with trifluoromethanesulfonic acid and methanesulfonic acid were proposed to take the place of the conventional hydrogen fluoride method and came to be used frequently (Yajima, et al., J.C.S. Chem. Comm., p. 107 (1974)). More recently, a method by the use of trimethylsilyl-trifluoro-methanesulfonate (Yajima, et al., J.C.S. Chem. Comm., pp. 274-275 (1987)) was proposed and not only has it become a generally accepted idea that the final deprotection be carried out under a milder acidic condition so as not to damage the peptide chain during the synthesis, if possible, but also a more strongly selective group which is stable against temporary deprotection of .alpha.-amino protecting group but removable under a milder acidic condition at the time of the final deprotection is desirable for .omega.-carboxyl group.